Treatment of Pneumocystis Jirovecii Pneumonia (PCP)
Trimethoprim-sulfamethoxazole (TMP-SMX) is the first-line treatment for Pneumocystis jirovecii pneumonia, administered at 15-20 mg/kg/day of TMP component in 3-4 divided doses for 14-21 days. 1
Diagnosis
- Bronchoalveolar lavage (BAL) is the gold standard diagnostic procedure with sensitivity of 87-95%
- Positive quantitative PCR (>1450 copies/ml) from BAL should trigger immediate treatment 2
- Treatment should be initiated before bronchoscopy and BAL if clinical suspicion is high based on:
- Characteristic radiographic pattern
- Elevated serum LDH
- Respiratory symptoms in immunocompromised patients
First-Line Treatment
Dosing Options:
- Standard dose: TMP 15-20 mg/kg/day with SMX 75-100 mg/kg/day in 3-4 divided doses for 14-21 days 1, 3
- Lower dose option: Recent evidence suggests TMP 10 mg/kg/day with SMX 50 mg/kg/day may be equally effective with fewer adverse events 4, 5, 6
Weight-based dosing guide for standard dose:
| Weight (kg) | Dose (every 6 hours) |
|---|---|
| 32 | 2 tablets or 1 DS |
| 48 | 3 tablets or 1½ DS |
| 64 | 4 tablets or 2 DS |
| 80 | 5 tablets or 2½ DS |
Alternative Treatments (for TMP-SMX intolerance)
- Clindamycin plus primaquine - preferred alternative for TMP-SMX intolerance 2, 1
- Atovaquone - 750 mg PO twice daily with food for 21 days 7
- Dapsone plus trimethoprim 1
- Aerosolized pentamidine 1
Adjunctive Therapy
- Corticosteroids are indicated for moderate to severe PCP (PaO2 <70 mmHg or A-a gradient >35 mmHg)
- Recommended regimen: Prednisone 40 mg twice daily for 5 days, then 40 mg daily for 5 days, then 20 mg daily for 11 days
- Corticosteroids should be started within 72 hours of PCP treatment for maximum benefit
- In non-HIV patients with critical respiratory insufficiency, corticosteroids should be considered on an individual basis 2
Special Populations
HIV Patients
- TMP-SMX is first-line therapy
- Higher rate of adverse reactions to TMP-SMX (40-65%) compared to non-HIV patients 2
- Corticosteroids strongly recommended for moderate-severe disease
Children
- TMP-SMX remains first-line therapy
- Dosing: TMP 15-20 mg/kg/day with SMX 75-100 mg/kg/day in 3-4 divided doses 2, 3
- Lower rate of adverse reactions to TMP-SMX (15%) compared to adults 2
Neutropenic Patients
- If PCP is suspected in febrile neutropenic patients, treatment should be initiated promptly 2
- Consider combination therapy with caspofungin and TMP-SMX in difficult cases 8
Prophylaxis
- Primary prophylaxis: Indicated for HIV patients with CD4+ count <200 cells/μL and other high-risk immunocompromised patients 2, 1
- Secondary prophylaxis: Essential after successful treatment to prevent recurrence 2, 1
- Preferred regimen: TMP-SMX (one double-strength tablet daily or three times weekly) 2, 1
- Alternative regimens: Aerosolized pentamidine, dapsone, or atovaquone 1
Monitoring and Adverse Effects
Common adverse reactions to TMP-SMX:
- Dermatologic: Rash (most common), Stevens-Johnson syndrome (rare)
- Hematologic: Leukopenia, thrombocytopenia
- Hepatic: Elevated liver enzymes, cholestatic hepatitis
- Renal: Decreased creatinine clearance
- Electrolyte: Hyperkalemia, hyponatremia
Dose adjustment for renal impairment:
- CrCl >30 mL/min: Standard regimen
- CrCl 15-30 mL/min: Half the usual regimen
- CrCl <15 mL/min: Not recommended 3
Treatment Duration
- Standard duration: 14-21 days 1, 3
- Consider longer treatment for severe cases or immunocompromised patients without HIV
Clinical Pearls
- Treatment should never be delayed if PCP is clinically suspected in high-risk patients
- Low-dose TMP-SMX (TMP 10 mg/kg/day) may provide similar efficacy with significantly fewer adverse events 5, 6
- Absorption of atovaquone is significantly increased when taken with food; failure to do so may result in treatment failure 7
- Combination of caspofungin with TMP-SMX may provide enhanced efficacy in difficult-to-treat cases 8